NEUROMUSCULAR BLOCKADE REVERSAL PRACTICE Julia lienesch & carrie mcmahon Gonzaga university PROVIDENCE SACRED HEART MEDICAL CENTER MARCH 20, 2014

STATEMENT OF THE PROBLEM Residual neuromuscular blockade and its management are well-established topics in current literature The incidence of residual blockade has not significantly declined even with the introduction of intermediate acting paralytics From 2000-2008, 15 studies revealed 20-65% of postoperative incidence TOFR <0.9 Associated with hypoxia, weakness, aspiration, impairment of the hypoxic ventilatory drive, and respiratory failure

RESIDUAL BLOCKADE DEFINITION TOFR of < 0.9 Clinical signs and symptoms of muscle weakness in the postoperative period Evolution of TOFR standard for extubation 0.70.8currently 0.9 Increased respiratory events, pharyngeal dysfunction, and aspiration risk with TOFR <0.9 (Eriksson et al, 1997)

PURPOSE STATEMENT “The purpose of this study was to assess, through survey, current practices among CRNAs in states from various regions regarding the use of reversal agents after pharmacologic neuromuscular blockade.”

RESEARCH QUESTIONS To what degree are reversal agents being given by CRNAs after the administration of neuromuscular blocking agents? What are the benefits and risks of neuromuscular blockade reversal? What factors influence CRNAs’ management of neuromuscular blockade reversal? How is the dose of reversal agent determined?

REVIEW OF LITERATURE MONITORING Acceleromyography monitoring gold standard Tactile fade lost at TOFR 0.3-0.4 5-second head lift possible at TOFR of <0.6 Pharyngeal tissue and upper esophageal sphincter dysfunction at TOFR 0.6-0.9  aspiration risk Murphy et al. (2008) Compared acceleromyography to conventional tactile TOF TOFR ≤0.9 in PACU: 4.5% acceleromyography vs 30% conventional, P <0.0001 TOFR <0.7 in PACU: 0% acceleromyography vs 13.3% conventional, P<0.001 Acceleromyography had less respiratory events in PACU

REVIEW OF LITERATURE MONITORING Clinical Tests Tidal Volume: recovery of spontaneous breathing Not reliable. Unchanged even when peripheral muscles are fully paralyzed. Vital Capacity: ability to take deep breaths Not sensitive enough. Unchanged with significant levels of paralysis at peripheral muscles. Head or leg lift test >5 s Not sensitive enough. Corresponds to TOFR >0.4. Useful to determine the optimal timing of reversal. Tongue depressor test Probably the most reliable clinical test. Corresponds to TOFR >0.8-0.9. Difficult to implement routinely. (Plaud et al, 2010)

REVIEW OF LITERATURE MONITORING Ulnar nerve superior site for planning emergence: Less likelihood of direct muscle stimulation Increased margin of safety as slower recovery vs diaphragm 5-fold increased risk of residual block when monitoring at eye Placement Electrode placement 2-6cm apart

REVIEW OF LITERATURE TIMING Debaene, Plaud, Dilly, & Donati (2003) Single dose of intermediate acting paralytic to 526 patients No reversal and > two hours post-administration 16% TOFR of <0.7 and 45% TOFR <0.9 in PACU Fuchs-Buder et al. (2010) Addressed neostigmine dose for shallow levels of paralysis Normal doses of neostigmine can produce paradoxical weakness at shallow residual paralysis (Caldwell, 1995) Groups with TOFR 0.4 and 0.6 given neostigmine 0.01, 0.02, 0.03 mg/kg, or none Reversal at TOFR 0.4-0.6 with neostigmine 0.02 mg/kg produced successful reversal within 10 minutes

REVIEW OF LITERATURE TIMING Kim et al. (2004) Administered neostigmine 0.07 mg/kg to surgical patients at a TOF of 1,2,3,4 Median times from neostigmine reversal administration until a TOFR of 0.9 TOF count 1 – 28.6minutes TOF count 2 – 22.6 minutes TOF count 3 – 15.6 minutes TOF count 4 – 9.7 minutes Authors recommend a TOF count of 4 for adequate reversal from rocuronium within 15 minutes Thilen et al. (2012) Every 10 minutes since paralytic dose = 10% less residual block

REVIEW OF LITERATURE NEOSTIGMINE DOSING TOF 4/4 with minimal fade: 0.015-0.025 mg/kg TOF 2-3/4: 0.04-0.05 mg/kg Dosing >0.07 mg/kg unlikely to achieve additional effect (Kopman & Eikermann, 2009) Avoiding blanket full reversal of light paralysis will minimize paradoxical weakness effect, risk for cholinergic crisis, and side effects Most effective reversal when given >15-20 minutes prior to extubation (Brull & Murphy, 2010)

REVIEW OF LITERATURE PONV SIDE EFFECT King et al. (1988) said Yes to PONV 38 orthopedic patients: Neostigmine 2.5mg/Atropine 1.2mg, 68% PONV compared with 32% at 24hr postop, (P<0.01) Joshi et al. (1999) said No difference 100 ambulatory surgery, Neostigmine 2.5mg/Robinul 0.5mg, (P<0.05) Hovorka et al. (1997) said No difference DB*, 162 hysterectomy cases. Neostigmine 2mg/Robinul 0.4mg (P<0.05) Cheng et al. (2005) said No difference Lit review, 933 patients, compared Neostigmine 2.5 vs 1.5mg doses and Robinul vs Atropine (P=0.08) Lovstad et al. (2001) said Yes to nausea DB, 90 lap-gyn cases, Mivacurium, Neostigmine 0.05mg/kg + Robinul 0.01mg/kg. (P=0.03). First 6hrs, 30% vs 11% nausea. No difference in vomiting. *(DB=double blind)

METHODOLOGY Qualitative study Online survey utilizing SurveyMonkey Survey distributed via state CRNA organizations Participants 289 CRNA survey participants Participating states: WA, AZ, NC, MD

FINDINGS REVERSAL AND TIME

FINDINGS REVERSAL AND TIME

FINDINGS REVERSAL AND TIME

FINDINGS REVERSAL AND TIME

FINDINGS TOP 3 FACTORS

FINDINGS PATIENT FACTORS

FINDINGS SIDE EFFECTS

FINDINGS MONITORING

RECOMMENDATIONS Time from last paralytic dose is not an adequate determinant of residual blockade Monitoring of blockade should be standard practice Acceleromyography superior as tactile fade lost at TOFR of 0.4 Not all patients need a full reversal dose Risk for paradoxical weakness and increased side effects Majority can benefit from a partial reversal dose Increased PONV is inconclusive and appears to be dose-dependent Faster recovery after reversal with increasing TOF count Allow 15-20 minutes after reversal for maximal effect

REFERENCES Brull, S.J., & Murphy, G.S. (2010). Residual neuromuscular block: lessons unlearned. Part II: methods to reduce the risk of residual weakness. Anesthesia and Analgesia, 111(1), 129-140. Cheng, C., Sessler, D. I., & Apfel, C. C. (2005). Does neostigmine administration produce a clinically important increase in postoperative nausea and vomiting? Anesthesia & Analgesia, 101, 1349-55. Debaene, B., Plaud, B., Dilly, M., & Donati, F. (2003). Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology, 98(5), 1042-1048. Retrieved from http://journals.lww.com/anesthesiology/Fulltext/2003/05000/Residual_Paralysis_in_the_PACU_after_a_Single.4.aspx Eriksson, L. I., Sundman, E., Olsson, R., Nilsson, L., Witt, H., Ekberg, O., & Kuylenstierna, R. (1997). Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: Simultaneous videomanometry and mechanomyography of awake human volunteers. Anesthesiology, 87(5), 1035-1043. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9366453 Fuchs-Buder, T., Meistelman, C., Alla, F., Grandjean, A., Wuthrich, Y., & Donati, F. (2010). Antagonism of low degrees of Atracurium-induced neuromuscular blockade. Anesthesiology, 112(1), 34-40.

REFERENCES Hovorka, J., Korttila, K., Nelskyla, K., Soikkeli, A., Sarvela, J., Paatero, H., ... Yli-Hankala, A. (1997). Reversal of neuromuscular blockade with neostigmine has no effect on the incidence or severity of postoperative nausea and vomiting. Anesthesia & Analgesia, 85, 1359-61. Joshi, G. P., Garg, S. A., Hailey, A., & Yu, S. Y. (1999). The effects of antagonizing residual neuromuscular blockade by neostigmine and glycopyrrolate on nausea and vomiting after ambulatory surgery. Anesthesia & Analgesia, 89, 628-31. Kim, K., Cheong, M., Lee, H., Lee, J. (2004) Tactile assessment for the reversibility of rocuronium induced neuromuscular blockade during propofol or sevoflurane anesthesia. Anesthesia Analgesia, 99, 1080-1085. King, M. T., Milazkiewicz, R., Carli, F., & Deacock, A. R. (1988). Influence of neostigmine on postoperative vomiting. British Journal of Anaesthesia, 61, 403-6. Kopman, A.F., & Eikermann, M. (2009). Antagonism of non-depolarising neuromuscular block: current practice. Anaesthesia, 64, 22-30.

REFERENCES Lovstad, R. Z., Thagaard, K. S., Berner, N. S., & Raeder, J. C. (2001). Neostigmine 5mcg/kg with glycopyrrolate increases postoperative nausea in women after laparoscopic gynaecological surgery. Acta Anaesthesiologica, 45, 495-500. Murphy, G. S., Szokol, J. W., Marymont, J. H., Greenberg, S. B., Avram, M. J., Vender, J. S., & Nisman, M. (2008). Intraoperative Acceleromyographic Monitoring Reduces the Risk of Residual Neuromuscular Blockade and Adverse Respiratory Events in the Postanesthesia Care Unit. Anesthesiology, 109, 389-398. Plaud, B., Debane, B., Donati, F., Marty, J. (2010) Residual paralysis after emergence from anesthesia. Anesthesiology, 112(4), 1013-1022. Thilen, S. R., Hansen, B. E., Ramaiah, R., Kent, C. D., Treggiari, M. M., & Bhananker, S. M. (2012). Intraoperative neuromuscular monitoring site and residual paralysis. Anesthesiology, 117, 964-972.